A double mutation of MBP83–99 peptide induces IL-4 responses and antagonizes IFN-γ responses

Katsara, Maria; Yuriev, Elizabeth; Ramsland, Paul A.; Deraos, George; Tselios, Theodore; Matsoukas, John; Apostolopoulos, Vasso

doi:10.1016/j.jneuroim.2008.06.013

Cited by 35 publications

(55 citation statements)

References 43 publications

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“…The y axis contains the relative signal at 195 nm the helical conformation, and they point outward from the MHC complex; these are the positions that MHC presents to the T cell. Mutation of these positions in the MBP85-99 epitope lead to altered immunological response [52,53].…”

Section: Myelin-derived or Myelin-mimicking Peptides Of Potential Relmentioning

confidence: 99%

Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments

Tuusa

Raasakka

Ruskamo

et al. 2017

Mult Scler Demyelinating Disord

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Background: Despite intense research, the causes of various neurological diseases remain enigmatic to date. A role for viral or bacterial infection and associated molecular mimicry has frequently been suggested in the etiology of neurological diseases, including demyelinating autoimmune disorders, such as multiple sclerosis. Pathogen mimics of myelin-derived autoimmune peptides have been described in the literature and shown to induce myelin autoimmune responses in animal models. Methods: We carried out a structural study on myelin-derived peptides, and mimics thereof from various pathogens, in aqueous and membrane-like environments, using conventional and synchrotron radiation circular dichroism spectroscopy. A total of 13 peptides from the literature were studied, and 290 circular dichroism spectra were analysed. In addition, peptide structure predictions and vesicle aggregation assays were performed.

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Section: Myelin-derived or Myelin-mimicking Peptides Of Potential Relmentioning

confidence: 99%

Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments

Tuusa

Raasakka

Ruskamo

et al. 2017

Mult Scler Demyelinating Disord

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“…It has been reported that this region of MBP is highly conserved in mammalian species including humans and rodents (Jones et al, 1992 with the TCR and substitution with alanine at these positions was able to inhibit the T-cell response in vitro (Karin et al, 1994, Katsara et al, 2008c. Cyclic peptides have been shown to be more stable in vivo with increased metabolic stability, potency, receptor selectivity and bioavailability relative to their linear counterparts (Matsoukas et al, 2005, Tselios et al, 2001, Katsara et al, 2006.…”

Section: Peptidesmentioning

confidence: 99%

Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation

Perera

Lees

Duffy

et al. 2015

Journal of Neuroimmunology

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“…Recently, the I-A s structure was deduced from the crystal structure of I-A u and a binding motif suffested. 52,53 MHC class II molecule is a noncovalently bonded heterodimer composed of α and b chains (α 1 , α 2 , b 1 and b 2 ) (Fig. 1).…”

Section: Mhc Class II Moleculesmentioning

confidence: 99%

MHC and MHC‑like molecules: Structural perspectives on the design of molecular vaccines

Apostolopoulos¹,

Yuriev²,

Lazoura³

et al. 2008

Human Vaccines

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© 2 0 0 8 L A N D E S B I O S C I E N C E . D O N O T D I S T R I B U T E .peptide-binding proteins as well as antigen processing molecules, such as TAP and tapasin. The MHC class II locus encodes heterodimeric peptide-binding proteins and proteins that modulate peptide loading onto MHC class II proteins in the lysosomal compartment, such as MHC class II DM, -DQ and -DP. MHC class I proteins are expressed on all nucleated cells and MHC class II are found on only a few specialized cell types; B-cells, neutrophils, dendritic cells and thymic epithelial cells and can be induced on macrophages and human T cells. The MHC class III locus encodes for other immune components, i.e., complement components (C2, C4, factor B), cytokines (TNFα and TNFb) and HSP70. Stimulation of CD8 T CellsMHC, first described more than 70 years ago to control transplant rejection in mice, was initially termed H-2. There are three gene families for murine MHC class I: H-2K, H-2D and H-2L and for human MHC: HLA-A, HLA-B and HLA-C. The first step in CD8 + T cell generation is the uptake and presentation of peptides by antigen presenting cells through their MHC molecules. Peptides bound to MHC class I are usually endogenous and cytosolic although exogenous peptides may also be presented by MHC class I molecules. 4,5 Exogenous antigens are taken up by antigen presenting cells (APCs), primarily dendritic cells, into phagosomes and early and late endosomes and presented to MHC class II molecules. Numerous reports have demonstrated that in early endosomes some antigens can either degrade or escape out of the endosome into the cytosol and enter the proteasome. 4,5 Likewise, endogenous peptides are primarily generated in the cytosol by the proteasome. From this point, exogenous-and endogenous-derived peptides follow the same pathway. The proteasome consists of 24 subunits, half of which contain proteolytic activity. The proteasome degrades antigens (proteins) into small peptides which are released into the cytosol. The peptides are transported from the cytosol into the endoplasmic reticulum (ER) via the transporter associated with antigen processing (TAP1 and TAP2) by ATP. In the ER, peptides bind to the newly synthesized MHC class I molecules following the formation of a large multimeric complex which involves TAP, tapasin, calreticulin, calnexin and ER60. From the ER, the peptide-MHC class I complex is transported to the surface of APCs through the secretory pathway (Golgi) where the complex undergoes several posttranslational modifications. Then the peptide-MHC class I complexes expressed

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A double mutation of MBP83–99 peptide induces IL-4 responses and antagonizes IFN-γ responses

Cited by 35 publications

References 43 publications

Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments

Myelin-derived and putative molecular mimic peptides share structural properties in aqueous and membrane-like environments

Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation

MHC and MHC‑like molecules: Structural perspectives on the design of molecular vaccines

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